3.3. Development and Characterization of the FFS

Colloidal FFSs were developed using a 2² full factorial design with a central point to evaluate the influence of the independent variables (PVA and PVP concentration) on the development of the FFS loaded with SEEU and SETM. The complete factorial design matrices with coded and uncoded values for each factor are summarized in Table 9. The trials were randomized to reduce bias.

Concentrations (%) and coded values used in the 2² full factorial designs for developing the FFS loaded with SEEU and SETM.

F1 = Formulation 1. F2 = Formulation 2. F3 = Formulation 3. F4 = Formulation 4. F5 = Formulation 5. CP = Central point.

Methylparaben (0.1%) was heated in distilled water (q.s.p. 100%) to 80 °C. After natural cooling to room temperature, PVA (2.5, 3.5, or 4.5%) was dispersed in the solution through constant agitation for 2 h (Phase A). Simultaneously, PVP (2.5, 3.5, or 4.5%) was dispersed in 17.5% ethanol P.A. (Phase B), and the extracts (7.81% SEEU + 3.90% SETM) were dispersed in 12.5% ethanol 20° GL (Phase C). Phases B and C were magnetically stirred at room temperature for 2 h and added to Phase A through dripping. This was followed by the addition of imidazolidinyl urea solution (0.3%). After incorporation, agitation was maintained for 16 h at room temperature. The FFS was stored in a pump airless bottle equipped with a metered dose valve until physical–chemical characterization.

The control formulations (C1–C5), corresponding to each FFS, were prepared as described above, but without the addition of the extract.

Five healthy men and five healthy women, aged between 20 and 40 years, with no history of skin diseases, were selected for organoleptic evaluation according to the protocol approved by the ethics committee for research involving human beings of Universidade Paranaense (5,832,179).

Approximately 0.3 mL of each FFS (amount corresponding to the volume delivered after each valve actuation) was applied to the back of the hand of the volunteer. The participants filled out a form indicating the drying time of the formulation (in minutes), adhesion, and appearance of the FFS. The film’s adhesion, appearance, clarity, shine, and transparency after drying were graded on scores. As parameters for bonding, 1—adhesive and 2—non-adhesive were used. As parameters for appearance, 1—shiny and transparent; 2—transparent, but without glare; 3—transparent, but flaky; 4—whitish film; 5—ruddy and shiny; 6—reddish but dull; and 7—reddish but scaly were used [74].

The pH of the FFS was determined in triplicate at 25 ± 1 °C using a calibrated digital potentiometer (Ionlab^®, pHB 500, Araucária, Brazil).

The volume of the FFS delivered after each valve actuation was determined using an analytical balance (Gehaka^®, AG-200, São Paulo, Brazil). Subsequently, the mean and standard deviation of 10 measurements were calculated. The volume of FFS delivered was calculated using Equation (2):

where A_L: volume of solution delivered at each activation; W_t: weight of the formulation after each actuation; W₀: initial weight of the formulation, before activation; D_n: density of the formulation [4].

Viscosity was determined using a Brookfield Digital viscometer (QUIMIS^®, Q860M26, Diadema, Brazil) equipped with a spindle No. 2, at 25 °C, in the range of 1 to 40 rpm [75].